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Eutrophication remains a persistent water quality issue throughout much of the United States, leading to changes to ecosystem health in valuable coastal habitats. Oysters help to buffer against eutrophication by removing nitrogen from the water column by feeding on phytoplankton and other seston, a process referred to as "bioextraction". Recent legislation in Texas has allowed oysters to be grown off-bottom (suspended in cages). To understand the connections between bioextraction and off-bottom oyster aquaculture, the Assessment of Estuarine Trophic Status (ASSETS) model was applied, indicating nutrient-related degradation of water quality. The Farm Aquaculture Resource Model (FARM) was used to determine that a typical oyster farm can remove about 4900-7100 lb. N yr -1 , with an approximate value of $41,966 to $232,511 based on engineered (wastewater treatment plant) technologies. A promising and innovative nutrient management strategy, bivalve mariculture can be utilized as an additional strategy complementary to existing nutrient management strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The practice of hormone therapy is crucial in aligning secondary sex characteristics with the gender identity of transgender adults. This study examines the effects of a commonly used injectable hormone combination, specifically estradiol enanthate with dihydroxyprogesterone acetophenide (EEn/DHPA), on serum hormonal levels and self-reported satisfaction with breast development in transwomen. Our research focused on a retrospective longitudinal study involving a large cohort of transwomen evaluated between 2020 and 2022, comprising 101 participants. We assessed serum levels of estradiol (E2), testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), comparing the EEn/DHPA hormonal regimen with other combined estrogen-progestogen (CEP) therapies. Additionally, a subset of 43 transwomen completed a 5-question survey to evaluate self-reported satisfaction with breast development using Tanner scales. Our findings indicated that participants using the EEn/DHPA regimen exhibited significantly higher serum E2 levels (mean: 186 pg/mL ± 32 pg/mL) than those using other therapies (62 ± 7 pg/mL), along with lower FSH levels, but no significant differences in T and LH levels. Concerning satisfaction with breast development, 76% reported increased fulfillment with breast augmentation while using EEn/DHPA. These results suggest that an injectable, low-cost EEn/DHPA administered every three weeks could serve as an alternative feminizing regimen, particularly considering the extensive long-term experience of the local transgender community. Further longitudinal studies on the efficacy of feminizing-body effects and endovascular risks of various parenteral CEP types are warranted to improve primary healthcare provision for transgender persons.

Cellular behavior is continuously influenced by mechanical forces. These forces span the cytoskeleton and reach the nucleus, where they trigger mechanotransduction pathways that regulate downstream biochemical events. Therefore, the nucleus has emerged as a regulator of cellular response to mechanical stimuli. Cell cycle progression is regulated by cyclin-CDK complexes. Recent studies demonstrated these biochemical pathways are influenced by mechanical signals, highlighting the interdependence of cellular mechanics and cell cycle regulation. In particular, the transition from G2 to mitosis (G2-M) shows significant changes in nuclear structure and organization, ranging from nuclear pore complex (NPC) and nuclear lamina disassembly to chromosome condensation. The remodeling of these mechanically active nuclear components indicates that mitotic entry is particularly sensitive to forces. Here, we address how mechanical forces crosstalk with the nucleus to determine the timing and efficiency of the G2-M transition. Finally, we discuss how the deregulation of nuclear mechanics has consequences for mitosis.

Background & Aims: Gender-affirming hormone therapy (GAHT) is essential for transgender individuals seeking body modifications. For transfeminine people assigned male at birth, GAHT typically involves a combination of antiandrogens and estrogens. Despite its importance, the scientific literature presents inconsistencies regarding the effects of these hormones on nutritional status, body composition, and biochemical markers. This study aims to evaluate the impact of estradiol enanthate and dihydroxyprogesterone acetophenide (E2EN/DHPA) hormonal treatment, in conjunction with resistive physical exercise, on body composition and metabolic profiles., Methods: Twenty-eight male rats were divided into three groups: MO (control group, n = 8), receiving sesame oil vehicle; MH (n = 11), receiving E2EN/DHPA; and MEH (n = 9), receiving E2EN/DHPA along with physical exercise. The hormonal treatment was administered every ten days for two months, while the exercise regimen involved stair climbing with progressively increasing weights, performed five times weekly for seven weeks. Evaluated parameters included body mass index (BMI), body composition (fat and lean mass), bone mineral density (BMD), and lipid profile (triglycerides, HDL-C, LDL-C)., Results: The rats that received E2EN/DHPA showed significant changes in body composition and BMI, regardless of exercise. The MH group had increased body fat, while both the MH and MEH groups had decreased bone area and mineral content. However, BMD remained the same across all groups. Elevated triglyceride levels were observed, and the MEH group also had reduced LDL-C levels. HDL-C levels did not show significant variation., Conclusion: The study's findings show similarities to changes seen in transfeminine individuals undergoing GAHT with estrogen and antiandrogens. These changes include decreased muscle mass, increased body fat, preserved bone mineral density, and elevated triglycerides. The study also found that resistance exercise positively impacted lipid profiles, particularly in reducing LDL-C. These results highlight the need for further research and comparative trials on hormone therapy regimens., Competing Interests: Declaration of competing interest The authors declare no commercial or financial affiliations that could be construed as a potential conflict of interest affecting the research presented in this paper., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Introduction: The study aims to analyze scientific publications on the association between social networks, social relationships, and social support for sports coaches. It seeks to identify the types and levels of social support provided by various agents, and to understand the impact of this support on coaches' wellbeing. The goal is to help coaches better utilize social support, thereby enhancing their quality of life, work, and performance., Methods: This study systematically reviewed 11 scientific articles to investigate the association between social support, social networks, and social relationships in sports coaches. It aimed to identify the types and levels of social support offered to coaches by family members, peers, and friends. Our research utilized the PRISMA guidelines for systematic reviews and assessed study quality using the STROBE Statement. Eligibility was determined by the PECOS criterion based on the search strategy terms., Results: Our findings indicate that social support has significant positive effects on sports coaches. It enhances selfcompassion, prevents burnout symptoms, boosts job and life satisfaction, and reduces stress levels. Organizational support, characterized by clear guidelines, guidance, and autonomy, yielded positive outcomes. Conversely, the absence of social support correlated with negative outcomes for coaches, including lower self-compassion, increased stress and burnout symptoms, reduced job and life satisfaction, and heightened work-family conflict. Coaches' social networks encompassed family members, peers, friends, and other sources, with friends perceived as the most influential. Maintaining an effective social support network is crucial for coaches' performance and psychological wellbeing., Discussion: This systematic review emphasizes the importance of social support for coaches in both their personal and professional lives, noting its positive effects and the negative consequences of its absence. Given the demanding nature of coaching, improving social support systems can enhance coaches' wellbeing and the success of sports activities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ferreira, Rodrigues, Sobreiro, Silva, Santos, Carvalho, Hernández Mendo and Rodrigues.)

Introduction: COPD and interstitial lung disease (ILD) are significant chronic respiratory disorders, impacting quality of life. Respiratory muscle roles and differences remain not entirely clear. The objective of the present study was to evaluate the degree of recruitment of the respiratory muscles and the work of breathing in COPD and ILD during exercise., Methods: We compared the sensory-mechanical relationships in COPD, ILD and healthy controls (n=20 each). They performed pulmonary function, noninvasive and invasive respiratory muscle strength, surface electromyography and work-of-breathing assessments., Results: COPD and ILD did not show lower static muscle strength compared to controls, but did show poor performance in the exercise test with increased transdiaphragmatic pressure ( P di ). In ILD, there was a higher increase in oesophageal pressure and a lower gastric pressure ( P ga ) on inspiration; in COPD, there was a significant increase in P ga on inspiration. In ILD, there is greater recruitment of accessory inspiratory muscles, whereas in COPD, there is marked use of both inspiratory and expiratory muscles. The neuromechanical inefficiency (increased neural respiratory drive without the corresponding tidal volume) was found in both diseases. In COPD, there is a considerable increase in elastic work to overcome intrinsic positive end-expiratory pressure (PEEP i ) and expiratory work of breathing, whereas in ILD, non-PEEP i elastic work of breathing is the highest part of the total work of breathing., Conclusions: Early and increased activity of the respiratory muscles and work-of-breathing components significantly contribute to dyspnoea, exercise intolerance and neuromechanical inefficiency of ventilation in COPD and ILD. The mechanisms of P di generation were different between diseases., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2024.)

This is the protocol for a Campbell systematic review. The objectives are as follows. The primary aim of this mixed methods review is to synthesise the available evidence regarding the effectiveness of restorative justice interventions (RJIs) for reducing offending and reoffending outcomes in children and young people. We are also particularly interested in the impact of RJIs on children and young peoples' violent offending and violent reoffending. A second aim of the review is to examine whether the magnitude of effectiveness of RJIs may be influenced by study characteristics such as the population (e.g., age, ethnicity, or sex), the form of intervention (e.g., face-to-face mediation compared to family group conferencing), the place of delivery of the intervention (e.g., in independent office, in court), implementation (e.g., trained facilitators, dose, fidelity) and methodology (e.g., randomised controlled trial). The third aim of the review is to synthesise the qualitative evidence about RJ to develop a better contextual understanding of how these programmes may work and to elucidate factors that might increase the efficacy and implementation of RJ interventions. The specific research questions this systematic review aims to address are: (1) Do RJ interventions reduce children and young people's involvement in offending or reoffending relative to a comparison group? [RQ1]. (2) Is there variation in the impact of different RJ approaches on young people's involvement in offending or reoffending? [RQ2]. (3) Is there variation in the impact of RJIs on children and young people's offending or reoffending depending on the characteristics of the participants taking part in the RJI (e.g., sex, age, ethnicity)? [RQ3]. (4) What characteristics of RJIs, influence the effectiveness of RJIs for children and young people's offending and reoffending? [RQ4]. (5) What are the most notable barriers and facilitators, as reported by participants (e.g., the victims, children/young people, or mediators who have taken part in an evaluation of an RJI, or those children or young people who were meant to take part in an evaluation but ultimately did not), to the implementation of RJIs to reduce later offending or reoffending? [RQ5]., (© 2024 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Proliferating cells need to cope with extensive cytoskeletal and nuclear remodeling as they prepare to divide. These events are tightly regulated by the nuclear translocation of the cyclin B1-CDK1 complex, that is partly dependent on nuclear tension. Standard experimental approaches do not allow the manipulation of forces acting on cells in a time-resolved manner. Here, we describe a protocol that enables dynamic mechanical manipulation of single cells with high spatial and temporal resolution and its application in the context of cell division. In addition, we also outline a method for the manipulation of substrate stiffness using polyacrylamide hydrogels. Finally, we describe a static cell confinement setup, which can be used to study the impact of prolonged mechanical stimulation in populations of cells. Key features • Protocol for microfabrication of confinement devices. • Single-cell dynamic confinement coupled with high-resolution microscopy. • Static cell confinement protocol that can be combined with super-resolution STED microscopy. • Analysis of the mechanical control of mitotic entry in a time-resolved manner., Competing Interests: Competing interestsThe authors have no competing interests., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY-NC license.)

Accurate centrosome separation and positioning during early mitosis relies on force-generating mechanisms regulated by a combination of extracellular, cytoplasmic, and nuclear cues. The identity of the nuclear cues involved in this process remains largely unknown. Here, we investigate how the prophase nucleus contributes to centrosome positioning during the initial stages of mitosis, using a combination of cell micropatterning, high-resolution live-cell imaging, and quantitative 3D cellular reconstruction. We show that in untransformed RPE-1 cells, centrosome positioning is regulated by a nuclear signal, independently of external cues. This nuclear mechanism relies on the linker of nucleoskeleton and cytoskeleton complex that controls the timely loading of dynein on the nuclear envelope (NE), providing spatial cues for robust centrosome positioning on the shortest nuclear axis, before nuclear envelope permeabilization. Our results demonstrate how nuclear-cytoskeletal coupling maintains a robust centrosome positioning mechanism to ensure efficient mitotic spindle assembly., (© 2024 Lima et al.)

Background: The golden mussel (Limnoperna fortunei) is a highly invasive species that causes environmental and socioeconomic losses in invaded areas. Reference genomes have proven to be a valuable resource for studying the biology of invasive species. While the current golden mussel genome has been useful for identifying new genes, its high fragmentation hinders some applications., Findings: In this study, we provide the first chromosome-level reference genome for the golden mussel. The genome was built using PacBio HiFi, 10X, and Hi-C sequencing data. The final assembly contains 99.4% of its total length assembled to the 15 chromosomes of the species and a scaffold N50 of 97.05 Mb. A total of 34,862 protein-coding genes were predicted, of which 84.7% were functionally annotated. A significant (6.48%) proportion of the genome was found to be in a hemizygous state. Using the new genome, we have performed a genome-wide characterization of the Doublesex and Mab-3 related transcription factor gene family, which has been proposed as a target for population control strategies in other species., Conclusions: From the applied research perspective, a higher-quality genome will support genome editing with the aim of developing biotechnology-based solutions to control invasion. From the basic research perspective, the new genome is a high-quality reference for molecular evolutionary studies of Mytilida and other Lophotrochozoa, and it may be used as a reference for future resequencing studies to assess genomic variation among different golden mussel populations, unveiling potential routes of dispersion and helping to establish better control policies., (© The Author(s) 2023. Published by Oxford University Press GigaScience.)

As cells prepare to divide, they must ensure that enough space is available to assemble the mitotic machinery without perturbing tissue homeostasis. To do so, cells undergo a series of biochemical reactions regulated by cyclin B1-CDK1 that trigger cytoskeletal reorganization and ensure the coordination of cytoplasmic and nuclear events. Along with the biochemical events that control mitotic entry, mechanical forces have recently emerged as important players in cell-cycle regulation. However, the exact link between mechanical forces and the biochemical pathways that control mitotic progression remains unknown. Here, we identify a tension-dependent signal on the nucleus that sets the time for nuclear envelope permeabilization (NEP) and mitotic entry. This signal relies on actomyosin contractility, which unfolds the nucleus during the G2-M transition, activating the stretch-sensitive cPLA2 on the nuclear envelope and regulating the nuclear translocation of cyclin B1. Our data demonstrate how nuclear tension during the G2-M transition contributes to timely and efficient mitotic spindle assembly and prevents chromosomal instability., (© 2022 Dantas et al.)

Climate change will expose the food-producing sector to a range of challenges. Inland aquaculture farms are particularly vulnerable, due to the difficulty in changing their location, and therefore require specific tools to predict the influence of direct and indirect effects on production, environment and economic feasibility. The objective of our study was to apply a simple set of models to produce a set of growth, risk and suitability maps for stakeholders within the common carp sector in Poland, to assist decision-making under two different scenarios of climate change: a moderate situation (RCP 4.5) and an extreme situation (RCP 8.5). We used present (2000-2019) and future projections (2080-2099) for water surface temperature based on land surface temperature data from regionally downscaled climate models to draw maps to: (i) show optimal temperature conditions for carp growth, (ii) assess risk of disease outbreak caused by three important common carp pathogens: Cyprinid herpesvirus 3 (CyHV-3), carp oedema virus (CEV) and spring viremia of carp (SVCV) and (iii) predict potential suitability changes of carp farming in Poland. The study identified areas with the most and least favourable temperature conditions for carp growth, as well as those areas with the highest/lowest number of days with suitable temperatures for virus infection. These suitability maps showed the combined effect of direct and indirect effects of climate change projections under RCP 8.5 and RCP 4.5 scenarios. The approach applied herein will be of use worldwide for analysing the risks of temperature increase to land-based aquaculture, and the results presented are important for carp farmers in Poland and elsewhere, industry in general, and government stakeholders, to understand the direct and indirect effects of climate change on the triple bottom line of people, planet, and profit., (© 2022 Wiley-VCH GmbH.)

Accurate chromosome segregation requires a complete restructuring of cellular organization. Microtubules remodel to assemble a mitotic spindle and the actin cytoskeleton rearranges to form a stiff actomyosin cortex. These cytoplasmic events must be spatially and temporally coordinated with mitotic chromosome condensation and nuclear envelope permeabilization, in order to ensure mitotic timing and fidelity. Here, we discuss the main cytoskeletal and nuclear events that occur during mitotic entry in proliferating animal cells, focusing on their coordinated contribution for early mitotic spindle assembly. We will also explore recent progress in understanding their regulatory biochemical and mechanical pathways., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Objective: The precise coordination of respiratory muscles during exercise minimizes work of breathing and avoids exercise intolerance. Fibrotic interstitial lung disease (f-ILD) patients are exercise-intolerant. We assessed whether respiratory muscle incoordination and thoracoabdominal asynchrony (TAA) occur in f-ILD during exercise, and their relationship with pulmonary function and exercise performance., Methods: We compared breathing pattern, respiratory mechanics, TAA and respiratory muscle recruitment in 31 f-ILD patients and 31 healthy subjects at rest and during incremental cycle exercise. TAA was defined as phase angle (PhAng) >20°., Results: During exercise, when compared with controls, f-ILD patients presented increased and early recruitment of inspiratory rib cage muscle (p < 0.05), and an increase in PhAng, indicating TAA. TAA was more frequent in f-ILD patients than in controls, both at 50% of the maximum workload (42.3% vs. 10.7%, p = 0.01) and at the peak (53.8% vs. 23%, p = 0.02). Compared with f-ILD patients without TAA, f-ILD patients with TAA had lower lung volumes (forced vital capacity, p < 0.01), greater dyspnoea (Medical Research Council > 2 in 64.3%, p = 0.02), worse exercise performance (lower maximal work rate % predicted, p = 0.03; lower tidal volume, p = 0.03; greater desaturation and dyspnoea, p < 0.01) and presented higher oesophageal inspiratory pressures with lower gastric inspiratory pressures and higher recruitment of scalene (p < 0.05)., Conclusion: Exercise induces TAA and higher recruitment of inspiratory accessory muscle in ILD patients. TAA during exercise occurred in more severely restricted ILD patients and was associated with exertional dyspnoea, desaturation and limited exercise performance., (© 2021 Asian Pacific Society of Respirology.)

In preparation for mitosis, cells undergo extensive reorganization of the cytoskeleton and nucleus, so that chromosomes can be efficiently segregated into two daughter cells. Coordination of these cytoskeletal and nuclear events occurs through biochemical regulatory pathways, orchestrated by Cyclin-CDK activity. However, recent studies provide evidence that physical forces are also involved in the early steps of spindle assembly. Here, we will review how the crosstalk of physical forces and biochemical signals coordinates nuclear and cytoplasmic events during the G2-M transition, to ensure efficient spindle assembly and faithful chromosome segregation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dantas, Lima and Ferreira.)

Background: Patients with unilateral diaphragmatic paralysis (UDP) may present with dyspnoea without specific cause and limited ability to exercise. We aimed to investigate the diaphragm contraction mechanisms and nondiaphragmatic inspiratory muscle activation during exercise in patients with UDP, compared with healthy individuals., Methods: Pulmonary function, as well as volitional and nonvolitional inspiratory muscle strength were evaluated in 35 patients and in 20 healthy subjects. Respiratory pressures and electromyography of scalene and sternocleidomastoid muscles were continuously recorded during incremental maximal cardiopulmonary exercise testing until symptom limitation. Dyspnoea was assessed at rest, every 2 min during exercise and at the end of exercise with a modified Borg scale., Main Results: Inspiratory muscle strength measurements were significantly lower for patients in comparison to controls (all p<0.05). Patients achieved lower peak of exercise (lower oxygen consumption) compared to controls, with both gastric (-9.8±4.6 cmH 2 O versus 8.9±6.0 cmH 2 O) and transdiaphragmatic (6.5±5.5 cmH 2 O versus 26.9±10.9 cmH 2 O) pressures significantly lower, along with larger activation of both scalene (40±22% EMGmax versus 18±14% EMGmax) and sternocleidomastoid (34±22% EMGmax versus 14±8% EMGmax). In addition, the paralysis group presented significant differences in breathing pattern during exercise (lower tidal volume and higher respiratory rate) with more dyspnoea symptoms compared to the control group., Conclusion: The paralysis group presented with exercise limitation accompanied by impairment in transdiaphragmatic pressure generation and larger accessory inspiratory muscles activation compared to controls, thereby contributing to a neuromechanical dissociation and increased dyspnoea perception., Competing Interests: Conflict of interest: M. Caleffi Pereira has nothing to disclose. Conflict of interest: L.Z. Cardenas has nothing to disclose. Conflict of interest: J.G. Ferreira has nothing to disclose. Conflict of interest: V.C. Iamonti has nothing to disclose. Conflict of interest: P.V. Santana has nothing to disclose Conflict of interest: A. Apanavius has nothing to disclose. Conflict of interest: P. Caruso has nothing to disclose. Conflict of interest: A. Fernandez has nothing to disclose. Conflict of interest: C.R.R. de Carvalho has nothing to disclose. Conflict of interest: D. Langer has nothing to disclose. Conflict of interest: A.L.P. de Albuquerque has nothing to disclose., (Copyright ©ERS 2021.)

Cell division requires a dynamic reorganization of cytoskeletal and nuclear components. One essential step is the separation of centrosomes, which allows the assembly of a microtubule-based mitotic spindle. This has to be spatially and temporally coordinated with other events such as adhesion complex disengagement, assembly of an actin-rich cell cortex and nuclear envelope breakdown (NEB), to ensure chromosome segregation fidelity. Previous methodologies often focused on a single event and failed to provide an integrated view of the process. In this chapter, we describe a method to study mitosis with high resolution, by analyzing the dynamic interplay between centrosomes, nucleus, and cell membrane, using a combination of live-cell imaging and micromanipulation with custom-designed computational tools.

During the initial stages of mitosis, multiple mechanisms drive centrosome separation and positioning. How they are coordinated to promote centrosome migration to opposite sides of the nucleus remains unclear. Here, we present Trackosome, an open-source image analysis software for tracking centrosomes and reconstructing nuclear and cellular membranes, based on volumetric live-imaging data. The toolbox runs in MATLAB and provides a graphical user interface for easy access to the tracking and analysis algorithms. It provides detailed quantification of the spatiotemporal relationships between centrosomes, nuclear envelope and cellular membrane, and can also be used to measure the dynamic fluctuations of the nuclear envelope. These fluctuations are important because they are related to the mechanical forces exerted on the nucleus by its adjacent cytoskeletal structures. Unlike previous algorithms based on circular or elliptical approximations, Trackosome measures membrane movement in a model-free condition, making it viable for irregularly shaped nuclei. Using Trackosome, we demonstrate significant correlations between the movements of the centrosomes, and identify specific oscillation modes of the nuclear envelope. Overall, Trackosome is a powerful tool that can be used to help unravel new elements in the spatiotemporal dynamics of subcellular structures., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

During the initial stages of cell division, the cytoskeleton is extensively reorganized so that a bipolar mitotic spindle can be correctly assembled. This process occurs through the action of molecular motors, cytoskeletal networks, and the nucleus. How the combined activity of these different components is spatiotemporally regulated to ensure efficient spindle assembly remains unclear. To investigate how cell shape, cytoskeletal organization, and molecular motors cross-talk to regulate initial spindle assembly, we use a combination of micropatterning with high-resolution imaging and 3D cellular reconstruction. We show that during prophase, centrosomes and nucleus reorient so that centrosomes are positioned on the shortest nuclear axis at nuclear envelope (NE) breakdown. We also find that this orientation depends on a combination of centrosome movement controlled by Arp2/3-mediated regulation of microtubule dynamics and Dynein-generated forces on the NE that regulate nuclear reorientation. Finally, we observe this centrosome configuration favors the establishment of an initial bipolar spindle scaffold, facilitating chromosome capture and accurate segregation, without compromising division plane orientation.

Incorrect kinetochore-microtubule attachments during mitosis can lead to chromosomal instability, a hallmark of human cancers. Mitotic error correction relies on the kinesin-13 MCAK, a microtubule depolymerase whose activity in vitro is suppressed by α-tubulin detyrosination-a posttranslational modification enriched on long-lived microtubules. However, whether and how MCAK activity required for mitotic error correction is regulated by α-tubulin detyrosination remains unknown. Here we found that detyrosinated α-tubulin accumulates on correct, more stable, kinetochore-microtubule attachments. Experimental manipulation of tubulin tyrosine ligase (TTL) or carboxypeptidase (Vasohibins-SVBP) activities to constitutively increase α-tubulin detyrosination near kinetochores compromised efficient error correction, without affecting overall kinetochore microtubule stability. Rescue experiments indicate that MCAK centromeric activity was required and sufficient to correct the mitotic errors caused by excessive α-tubulin detyrosination independently of its global impact on microtubule dynamics. Thus, microtubules are not just passive elements during mitotic error correction, and the extent of α-tubulin detyrosination allows centromeric MCAK to discriminate correct vs. incorrect kinetochore-microtubule attachments, thereby promoting mitotic fidelity., (© 2020 Ferreira et al.)

Eutrophication is a challenge to coastal waters around the globe. In many places, nutrient reductions from land-based sources have not been sufficient to achieve desired water quality improvements. Bivalve shellfish have shown promise as an in-water strategy to complement land-based nutrient management. A local-scale production model was used to estimate oyster ( Crassostrea virginica ) harvest and bioextraction of nitrogen (N) in Great Bay Piscataqua River Estuary (GBP), New Hampshire, USA, because a system-scale ecological model was not available. Farm-scale N removal results (0.072 metric tons acre -1 year -1 ) were up-scaled to provide a system-wide removal estimate for current (0.61 metric tons year -1 ), and potential removal (2.35 metric tons year -1 ) at maximum possible expansion of licensed aquaculture areas. Restored reef N removal was included to provide a more complete picture. Nitrogen removal through reef sequestration was ~ 3 times that of aquaculture. Estimated reef-associated denitrification, based on previously reported rates, removed 0.19 metric tons N year -1 . When all oyster processes (aquaculture and reefs) were included, N removal was 0.33% and 0.54% of incoming N for current and expanded acres, respectively. An avoided cost approach, with wastewater treatment as the alternative management measure, was used to estimate the value of the N removed. The maximum economic value for aquaculture-based removal was $105,000 and $405,000 for current and expanded oyster areas, respectively. Combined aquaculture and reef restoration is suggested to maximize N reduction capacity while limiting use conflicts. Comparison of removal based on per oyster N content suggests much lower removal rates than model results, but model harvest estimates are similar to reported harvest. Though results are specific to GBP, the approach is transferable to estuaries that support bivalve aquaculture but do not have complex system-scale hydrodynamic or ecological models.

In late 2019, a novel coronavirus initially related to a cluster of severe pneumonia cases in China was identified. COVID-19 cases have rapidly spread to multiple countries worldwide. We present a typical laboratory confirmed case of COVID-19 pneumonia, that was hospitalized due to hypoxemia but did not require mechanical ventilation. Although initially the patient was evaluated with a favorable outcome, in the third week of the disease, the symptomatology deteriorated due to a massive hypertensive pneumothorax with no known previous risk factor. Since the first cases of COVID-19 have been described, pneumothorax was characterized as a potential, though uncommon, complication. It has been reported that diffuse alveolar injury caused by SARS-CoV-2 can cause alveolar rupture, produce air leakage and interstitial emphysema. Although uncommon, pneumothorax should be listed as a differential diagnosis for COVID-19 patients with sudden respiratory decompensation. As a life-threatening event, it requires prompt recognition and expeditious treatment.

According to the prevailing 'clock' model, chromosome decondensation and nuclear envelope reformation when cells exit mitosis are byproducts of Cdk1 inactivation at the metaphase-anaphase transition, controlled by the spindle assembly checkpoint. However, mitotic exit was recently shown to be a function of chromosome separation during anaphase, assisted by a midzone Aurora B phosphorylation gradient - the 'ruler' model. Here we found that Cdk1 remains active during anaphase due to ongoing APC/C Cdc20 - and APC/C Cdh1 -mediated degradation of B-type Cyclins in Drosophila and human cells. Failure to degrade B-type Cyclins during anaphase prevented mitotic exit in a Cdk1-dependent manner. Cyclin B1-Cdk1 localized at the spindle midzone in an Aurora B-dependent manner, with incompletely separated chromosomes showing the highest Cdk1 activity. Slowing down anaphase chromosome motion delayed Cyclin B1 degradation and mitotic exit in an Aurora B-dependent manner. Thus, a crosstalk between molecular 'rulers' and 'clocks' licenses mitotic exit only after proper chromosome separation., Competing Interests: OA, CC, LC, JF, BO, LF, JC, EM, TM, HM No competing interests declared, (© 2019, Afonso et al.)

Temporal and spatial trends of paralytic shellfish toxins (PSTs) in bivalves from Portuguese estuarine and coastal waters, and connectivity of bivalve toxicity among the harvest areas, were examined using long-term data from the national biotoxin monitoring programme. Data from 1994 to 2017 were chosen for commercial bivalve species sensitive to PSTs, and for production areas exhibiting recurrent episodes of bivalve toxicity. Mussels (Mytilus spp.) and cockles (Cerastoderma edule) from the Ria de Aveiro, Mondego estuary, Óbidos lagoon and Ria Formosa, and wedge clams (Donax trunculus) and surf clams (Spisula solida) from the coastal areas Aguda and Olhão were selected. Bivalve toxicity data point to higher incidents of PST episodes in autumn and winter, although in 2008 the toxicity of mussels and cockles in the three estuarine areas was registered in summer. Most likely, favourable oceanographic conditions triggered the bloom formation of Gymnodinium catenatum, which is the species responsible for paralytic shellfish poisoning in Portuguese waters. Episodes in the southern coast of Portugal were less recurrent, although values above the PST regulatory limit displayed also a seasonal signal with a peak between autumn and early winter. On the basis of the number of weeks per month that bivalves showed elevated toxicity values, a connectivity index was defined for the surveyed areas. High connectivity was obtained among Aveiro, Mondego and Óbidos, which are 180 km apart, suggesting that G. catenatum cells are imported from blooms formed or reaching the coastal waters adjacent to these systems. During episodes of elevated toxicity, toxin profiles in contaminated mussels and cockles were dominated by N-sulfocarbamoyl compounds, which are the major toxins produced by the toxic dinoflagellate G. catenatum. The identification of coupled systems relatively to bivalve toxicity has an impact on monitoring programmes and allows improved decision-making on closures of bivalve harvest areas affected by toxic algae., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The presence of aberrant number of centrioles is a recognized cause of aneuploidy and hallmark of cancer. Hence, centriole duplication needs to be tightly regulated. It has been proposed that centriole separation limits centrosome duplication. The mechanism driving centriole separation is poorly understood and little is known on how this is linked to centriole duplication. Here, we propose that actin-generated forces regulate centriole separation. By imposing geometric constraints via micropatterns, we were able to prove that precise acto-myosin force arrangements control direction, distance and time of centriole separation. Accordingly, inhibition of acto-myosin contractility impairs centriole separation. Alongside, we observed that organization of acto-myosin force modulates specifically the length of S-G2 phases of the cell cycle, PLK4 recruitment at the centrosome and centriole fidelity. These discoveries led us to suggest that acto-myosin forces might act in fundamental mechanisms of aneuploidy prevention.

Small airway and interstitial pulmonary involvements are prominent in chronic hypersensitivity pneumonitis (cHP). However, their roles on exercise limitation and the relationship with functional lung tests have not been studied in detail. Our aim was to evaluate exercise performance and its determinants in cHP. We evaluated maximal cardiopulmonary exercise testing performance in 28 cHP patients (forced vital capacity 57±17% pred) and 18 healthy controls during cycling. Patients had reduced exercise performance with lower peak oxygen production (16.6 (12.3-19.98) mL·kg -1 ·min -1 versus 25.1 (16.9-32.0), p=0.003), diminished breathing reserve (% maximal voluntary ventilation) (12 (6.4-34.8)% versus 41 (32.7-50.8)%, p<0.001) and hyperventilation (minute ventilation/carbon dioxide production slope 37±5 versus 31±4, p<0.001). All patients presented oxygen desaturation and augmented Borg dyspnoea scores (8 (5-10) versus 4 (1-7), p=0.004). The prevalence of dynamic hyperinflation was found in only 18% of patients. When comparing cHP patients with normal and low peak oxygen production (<84% pred, lower limit of normal), the latter exhibited a higher minute ventilation/carbon dioxide production slope (39±5.0 versus 34±3.6, p=0.004), lower tidal volume (0.84 (0.78-0.90) L versus 1.15 (0.97-1.67) L, p=0.002), and poorer physical functioning score on the Short form-36 health survey. Receiver operating characteristic curve analysis showed that reduced lung volumes (forced vital capacity %, total lung capacity % and diffusing capacity of the lung for carbon dioxide %) were high predictors of poor exercise capacity. Reduced exercise capacity was prevalent in patients because of ventilatory limitation and not due to dynamic hyperinflation. Reduced lung volumes were reliable predictors of lower performance during exercise., Competing Interests: Conflict of interest: Carlos Roberto Ribeiro Carvalho reports personal fees from Boehringer Ingelheim, outside the submitted work.

Background: Most patients with unilateral diaphragm paralysis (UDP) have unexplained dyspnea, exercise limitations, and reduction in inspiratory muscle capacity. We aimed to evaluate the generation of pressure in each hemidiaphragm separately and its contribution to overall inspiratory strength., Methods: Twenty-seven patients, 9 in right paralysis group (RP) and 18 in left paralysis group (LP), with forced vital capacity (FVC) < 80% pred, and 20 healthy controls (CG), with forced expiratory volume in 1 s (FEV 1 ) > 80% pred and FVC > 80% pred, were evaluated for lung function, maximal inspiratory (MIP) and expiratory (MEP) pressure measurements, diaphragm ultrasound, and transdiaphragmatic pressure during magnetic phrenic nerve stimulation (Pdi Tw )., Results: RP and LP had significant inspiratory muscle weakness compared to controls, detected by MIP (- 57.4 ± 16.9 for RP; - 67.1 ± 28.5 for LP and - 103.1 ± 30.4 cmH 2 O for CG) and also by Pdi TW (5.7 ± 4 for RP; 4.8 ± 2.3 for LP and 15.3 ± 5.7 cmH 2 O for CG). The Pdi Tw was reduced even when the non-paralyzed hemidiaphragm was stimulated, mainly due to the low contribution of gastric pressure (around 30%), regardless of whether the paralysis was in the right or left hemidiaphragm. On the other hand, in CG, esophagic and gastric pressures had similar contribution to the overall Pdi (around 50%). Comparing both paralyzed and non-paralyzed hemidiaphragms, the mobility during quiet and deep breathing, and thickness at functional residual capacity (FRC) and total lung capacity (TLC), were significantly reduced in paralyzed hemidiaphragm. In addition, thickness fraction was extremely diminished when contrasted with the non-paralyzed hemidiaphragm., Conclusions: In symptomatic patients with UDP, global inspiratory strength is reduced not only due to weakness in the paralyzed hemidiaphragm but also to impairment in the pressure generated by the non-paralyzed hemidiaphragm.

Objective: Evaluate the accuracy of criteria for diagnosing pressure overassistance during pressure support ventilation., Design: Prospective clinical study., Setting: Medical-surgical ICU., Patients: Adults under mechanical ventilation for 48 hours or more using pressure support ventilation and without any sedative for 6 hours or more. Overassistance was defined as the occurrence of work of breathing less than 0.3 J/L or 10% or more of ineffective inspiratory effort. Two alternative overassistance definitions were based on the occurrence of inspiratory esophageal pressure-time product of less than 50 cm H2O s/min or esophageal occlusion pressure of less than 1.5 cm H2O., Interventions: The pressure support was set to 20 cm H2O and decreased in 3-cm H2O steps down to 2 cm H2O., Measurements and Main Results: The following parameters were evaluated to diagnose overassistance: respiratory rate, tidal volume, minute ventilation, peripheral arterial oxygen saturation, rapid shallow breathing index, heart rate, mean arterial pressure, change in esophageal pressure during inspiration, and esophageal and airway occlusion pressure. In all definitions, the respiratory rate had the greatest accuracy for diagnosing overassistance (receiver operating characteristic area = 0.92; 0.91 and 0.76 for work of breathing, pressure-time product and esophageal occlusion pressure in definition, respectively) and always with a cutoff of 17 incursions per minute. In all definitions, a respiratory rate of less than or equal to 12 confirmed overassistance (100% specificity), whereas a respiratory rate of greater than or equal to 30 excluded overassistance (100% sensitivity)., Conclusion: A respiratory rate of 17 breaths/min is the parameter with the greatest accuracy for diagnosing overassistance. Respiratory rates of less than or equal to 12 or greater than or equal to 30 are useful clinical references to confirm or exclude pressure support overassistance.

Land-based management has reduced nutrient discharges; however, many coastal waterbodies remain impaired. Oyster "bioextraction" of nutrients and how oyster aquaculture might complement existing management measures in urban estuaries was examined in Long Island Sound, Connecticut. Eutrophication status, nutrient removal, and ecosystem service values were estimated using eutrophication, circulation, local- and ecosystem-scale models, and an avoided-costs valuation. System-scale modeling estimated that 1.31% and 2.68% of incoming nutrients could be removed by current and expanded production, respectively. Up-scaled local-scale results were similar to system-scale results, suggesting that this up-scaling method could be useful in bodies of water without circulation models. The value of removed nitrogen was estimated using alternative management costs (e.g., wastewater treatment) as representative, showing ecosystem service values of $8.5 and $470 million per year for current and maximum expanded production, respectively. These estimates are conservative; removal by clams in Connecticut, oysters and clams in New York, and denitrification are not included. Optimistically, the calculation of oyster-associated removal from all leases in both states (5% of bottom area) plus denitrification losses showed increases to 10%-30% of annual inputs, which would be higher if clams were included. Results are specific to Long Island Sound, but the approach is transferable to other urban estuaries.

Background: Thoracoabdominal asynchrony is the nonparallel motion of the ribcage and abdomen. It is estimated by using respiratory inductive plethysmography and, recently, using optoelectronic plethysmography; however the agreement of measurements between these 2 techniques is unknown. Therefore, the present study compared respiratory inductive plethysmography with optoelectronic plethysmography for measuring thoracoabdominal asynchrony to see if the measurements were similar or different., Methods: 27 individuals (9 healthy subjects, 9 patients with interstitial lung disease, and 9 with chronic obstructive pulmonary disease performed 2 cycle ergometer tests with respiratory inductive plethysmography or optoelectronic plethysmography in a random order. Thoracoabdominal asynchrony was evaluated at rest, and at 50% and 75% of maximal workload between the superior ribcage and abdomen using a phase angle., Results: Thoracoabdominal asynchrony values were very similar in both approaches not only at rest but also with exercise, with no statistical difference. There was a good correlation between the methods and the Phase angle values were within the limits of agreement in the Bland-Altman analysis., Conclusion: Thoracoabdominal asynchrony measured by optoelectronic plethysmography and respiratory inductive plethysmography results in similar values and has a satisfactory agreement at rest and even for different exercise intensities in these groups.

In the on-going quest to harvest near-infrared (NIR) photons for energy conversion applications, a novel family of neutral ruthenium(ii) sensitizers has been developed by cyclometalation of an azadipyrromethene chromophore. These rare examples of neutral ruthenium complexes based on polypyridine ligands exhibit an impressive panchromaticity achieved by the cyclometalation strategy, with strong light absorption in the 600-800 nm range that tails beyond 1100 nm in the terpyridine-based adducts. Evaluation of the potential for Dye-Sensitized Solar Cells (DSSC) and Organic Photovoltaic (OPV) applications is made through rationalization of the structure-property relationship by spectroscopic, electrochemical, X-ray structural and computational modelization investigations. Spectroscopic evidence for photo-induced charge injection into the conduction band of TiO2 is also provided.

The search for natural products and related analogs as potential anticancer agents has seen a significant growth worldwide. Since small sized propargylic diols can be found in nature and chemically synthesized, their evaluation against cancer cells has been of great interest, being a topic of relevance to be investigated. For this purpose, a scalable approach aiming at the synthesis of several propargylic diols and their bioactivity against seven tumor cell lines were evaluated. Interestingly, when the compound 1a, a natural product produced by fungus Clitocybe catinus, was tested in its racemic mixture a more effective activity was observed if compared when enantiopure R-1a or S-1a were tested separately., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In the present investigation, a collection of nineteen 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3H)-ones was synthesized and screened for their cytotoxic activity against a panel of three leukemia cancer cell lines. The compounds were prepared via ZrOCl2·8H2O catalyzed condensation reactions between phthalaldehydic acid and different acetophenones. The reactions were carried out free of solvent and the isobenzofuran-1(3H)-ones were obtained in good yields (80-92%). The identities of the synthesized compounds were confirmed upon IR and NMR ((1)H and (13)C) spectroscopy as well as high resolution mass spectrometry analyses. Structures of compounds 1, 4 and 16 were also investigated by X-ray analysis. The synthesized compounds were submitted to in vitro bioassays against HL-60, K562 and NALM6 cancer cell lines using MTT cytotoxicity assay. After 48h of treatment, twelve derivatives were able to reduce cell viability and presented IC50 values equal to or below 20μmolL(-1) against at least one of the evaluated lineages. The most active compound corresponded to 3-(3-methylphenyl-2-oxoethyl)isobenzofuran-1(3H)-one (18) (IC50 values obtained for HL-60, K562 and NALM6 were, respectively, 13.5μmolL(-1), 8.83μmolL(-1), and 5.24μmolL(-1)). In addition, compound 18 was capable of triggering apoptosis on NALM6 cells. All isobenzofuranones herein evaluated did not present cytotoxicity on peripheral blood mononuclear cells (PBMC), suggesting selective cytotoxic effect on leukemic cells. A computational study allowed prediction of pharmacokinetics and drug-likeness properties of the synthesized compounds. DFT calculations were performed to obtain the energy values of HOMO, LUMO, and dipole moments of isobenzofuranones., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In this study, our aims were to investigate transient receptor potential melastatin-8 channels (TRPM8) involvement in rotundifolone induced relaxation in the mesenteric artery and to increase the understanding of the role of these thermosensitive TRP channels in vascular tissue. Thus, message and protein levels of TRPM8 were measured by semi-quantitative PCR and western blotting in superior mesenteric arteries from 12 week-old Spague-Dawley (SD) rats. Isometric tension recordings evaluated the relaxant response in mesenteric rings were also performed. Additionally, the intracellular Ca2+ changes in mesenteric artery myocytes were measured using confocal microscopy. Using PCR and western blotting, both TRPM8 channel mRNA and protein expression was measured in SD rat mesenteric artery. Rotundifolone and menthol induced relaxation in the isolated superior mesenteric artery from SD rats and improved the relaxant response induced by cool temperatures. Also, this monoterpene induced an increase in transient intracellular Ca2+. These responses were significantly attenuated by pretreatment with capsazepine or BCTC, both TRPM8 channels blockers. The response induced by rotundifolone was not significantly attenuated by ruthenium red, a non-selective TRP channels blocker, or following capsaicin-mediated desensitization of TRPV1. Our findings suggest that rotundifolone induces relaxation by activating TRPM8 channels in rat superior mesenteric artery, more selectively than menthol, the classic TRPM8 agonist, and TRPM8 channels participates in vasodilatory pathways in isolated rat mesenteric arteries.

Profiles of paralytic shellfish toxins (PSTs) were examined in 405 composite samples of Mytilus spp., Cerastoderma edule, Donax trunculus and Spisula solida collected between 2007 and 2012 from natural production areas in two estuaries (Aveiro and Mondego), two coastal lagoons (Óbidos and Formosa), and three open coastal areas (Aguda, Comporta and Culatra). Toxin concentrations were obtained from the biotoxin monitoring programme database. Episodes of PST toxicity in Portugal have been associated with Gymnodinium catenatum blooms. Toxin profiles for each species showed no trend over the surveyed years. In general, profiles differ only slightly among areas, except for Óbidos. However, toxin profiles in bivalves varied between low and elevated toxicities, corresponding to below and above the PST regulatory limit, respectively. The ratio R1=(C1+2):B1, which were the main toxins produced by G. catenatum cells, decreased considerably between elevated and low toxicity cockles, indicating the elimination of C1+2 or conversion of compounds into B1. R2=[(dcSTX)+(dcGTX2+3)]:[(C1+2)+(B1)], which represents the ratio of minor to major toxins in G. catenatum cells, increased substantially in wedge clams (D. trunculus) of low toxicity and less markedly in cockles (C. edule) and mussels (Mytilus spp.). These differences are interpreted as the predominance of a biotransformation phase after exposure to the algal bloom. The toxin profile of surf clams (S. solida) was dominated by decarbamoyl compounds, reflecting intense biotransformation during exposure to blooms. The higher ratio R2 in low toxicity samples suggests that elimination of the produced decarbamoyl toxins was slower than biotransformation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)